Based on the hypothesis that activated E receptor (ER) functions via association with one or more transcription factors that bind directly to -105/-72 DNA, the following aims are proposed: Aim 1 seeks to define the DNA sequences necessary for repression of FSH beta by E; Aim 2 will identify the nuclear proteins that bind directly to the -105 to -72 bp region and determine how they interact with the activated ER; Aim 3 will use existing mutants of the ER to define the characteristics necessary for repression; and Aim 4 involves the production of transgenic mice that contain either wild-type or mutated ovine FSH beta genes to determine which binding sites in the -105/-72 sequence are critical for negative regulation in vivo.